tbuckley/cabot-search huggingface dataset:
Increasing ecological heterogeneity can constrain biopesticide resistance evolution
Authors: Rosie Mangan, Luc F. Bussière, Ricardo Antônio Polanczyk, Matthew C. Tinsley
Journal: Trends in Ecology & Evolution (2023)

Microbial biopesticides containing living parasites are valuable emerging crop protection technologies against insect pests, but they are vulnerable to resistance evolution. Fortunately, the fitness of alleles that provide resistance, including to parasites used in biopesticides, frequently depends on parasite identity and environmental conditions. This context-specificity suggests a sustainable approach to biopesticide resistance management through landscape diversification. To mitigate resistance risks, we advocate increasing the range of biopesticides available to farmers, whilst simultaneously encouraging other aspects of landscape-wide crop heterogeneity that can generate variable selection on resistance alleles. This approach requires agricultural stakeholders to prioritize diversity as well as efficiency, both within agricultural landscapes and the biocontrol marketplace.
RUNX1::ETO translocations must precede CSF3R mutations to promote acute myeloid leukemia development
Authors: Sarah A. Carratt, Garth L. Kong, Cody Coblentz, Zachary Schonrock, Lauren Maloney, Ben Weeder, Will Yashar, Rowan Callahan, Hunter Blaylock, Colin Coleman, Dan Coleman, Theodore P. Braun, Julia E. Maxson
Journal: Leukemia (2023)
Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis
Authors: Cristina de Dios, Xenia Abadin, Vicente Roca-Agujetas, Marina Jimenez-Martinez, Albert Morales, Ramon Trullas, Montserrat Mari, Anna Colell
Journal: Translational Neurodegeneration (2023)

Abstract Background Persistent inflammatory response in the brain can lead to tissue damage and neurodegeneration. In Alzheimer's disease (AD), there is an aberrant activation of inflammasomes, molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D (GSDMD), the executor of pyroptosis. However, the mechanisms underlying the sustained activation of inflammasomes in AD are largely unknown. We have previously shown that high brain cholesterol levels promote amyloid-β (Aβ) accumulation and oxidative stress. Here, we investigate whether these cholesterol-mediated changes may regulate the inflammasome pathway. Methods SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-soluble cholesterol complex. After exposure to lipopolysaccharide (LPS) plus muramyl dipeptide or Aβ, activation of the inflammasome pathway was analyzed by immunofluorescence, ELISA and immunoblotting analysis. Fluorescently-labeled Aβ was employed to monitor changes in microglia phagocytosis. Conditioned medium was used to study how microglia-neuron interrelationship modulates the inflammasome-mediated response. Results In activated microglia, cholesterol enrichment promoted the release of encapsulated IL-1β accompanied by a switch to a more neuroprotective phenotype, with increased phagocytic capacity and release of neurotrophic factors. In contrast, in SH-SY5Y cells, high cholesterol levels stimulated inflammasome assembly triggered by both bacterial toxins and Aβ peptides, resulting in GSDMD-mediated pyroptosis. Glutathione (GSH) ethyl ester treatment, which recovered the cholesterol-mediated depletion of mitochondrial GSH levels, significantly reduced the Aβ-induced oxidative stress in the neuronal cells, resulting in lower inflammasome activation and cell death. Furthermore, using conditioned media, we showed that neuronal pyroptosis affects the function of the cholesterol-enriched microglia, lowering its phagocytic activity and, therefore, the ability to degrade extracellular Aβ. Conclusions Changes in intracellular cholesterol levels differentially regulate the inflammasome-mediated immune response in microglia and neuronal cells. Given the microglia-neuron cross-talk in the brain, cholesterol modulation should be considered a potential therapeutic target for AD treatment, which may help to block the aberrant and chronic inflammation observed during the disease progression.
Combined targeting of CCL7 and Flt3L to promote the expansion and infiltration of cDC1s in tumors enhances T-cell activation and anti-PD-1 therapy effectiveness in NSCLC
Authors: Hong-Peng Dong, Ying Li, Zhen Tang, Peng Wang, Bo Zhong, Qian Chu, Dandan Lin
Journal: Cellular and Molecular Immunology (2023)
Functional restoration of a CFTR splicing mutation through RNA delivery of CRISPR adenine base editor
Authors: Simone Amistadi, Giulia Maule, Matteo Ciciani, Marjolein M. Ensinck, Liesbeth De Keersmaecker, Anabela S. Ramalho, Daniela Guidone, Martina Buccirossi, Luis J.V. Galietta, Marianne S. Carlon, Anna Cereseto
Journal: Molecular Therapy (2023)

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The 2789+5G>A CFTR mutation is a quite frequent defect causing an aberrant splicing and a non-functional CFTR protein. Here we used a CRISPR adenine base editing (ABE) approach to correct the mutation in the absence of DNA double-strand breaks (DSB). To select the strategy, we developed a minigene cellular model reproducing the 2789+5G>A splicing defect. We obtained up to 70% editing in the minigene model by adapting the ABE to the PAM sequence optimal for targeting 2789+5G>A with a SpCas9-NG (NG-ABE). Nonetheless, the on-target base correction was accompanied by secondary (bystander) A-to-G conversions in nearby nucleotides, which affected the wild-type CFTR splicing. To decrease the bystander edits, we used a specific ABE (NG-ABEmax), which was delivered as mRNA. The NG-ABEmax RNA approach was validated in patient-derived rectal organoids and bronchial epithelial cells showing sufficient gene correction to recover the CFTR function. Finally, in-depth sequencing revealed high editing precision genome-wide and allele-specific correction. Here we report the development of a base editing strategy to precisely repair the 2789+5G>A mutation resulting in restoration of the CFTR function, while reducing bystander and off-target activities.
A20 is a master switch of IL-33 signaling in macrophages and determines IL-33–induced lung immunity
Authors: Aurora Holgado, Zhuangzhuang Liu, Aigerim Aidarova, Christina Mueller, Mira Haegman, Yasmine Driege, Marja Kreike, Charlotte L. Scott, Inna S. Afonina, Rudi Beyaert
Journal: Journal of Allergy and Clinical Immunology (2023)
Re: Peter L. Sunaryo, Philip C. May, Sarah K. Holt, Matthew D. Sorensen, Robert M. Sweet, Jonathan D. Harper. Ureteral Strictures Following Ureteroscopy for Kidney Stone Disease: A Population-based Assessment. J Urol 2022;208:1268–75
Authors: Guido Giusti, Silvia Proietti, Franco Gaboardi
Journal: European Urology (2023)
Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis
Authors: Yahong Zhao, Jina Liu, Sha Liu, Panpan Yang, Yunyun Liang, Jinyu Ma, Susu Mao, Cheng Sun, Yumin Yang
Journal: Bioactive Materials (2023)

Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides (COS), implying that exosomes are involved in COS-induced peripheral nerve regeneration. In fact, exosomes derived from fibroblasts (f-EXOs) treated with COS significantly promoted axon extension and regeneration. Exosomal protein identification and functional studies, revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs. Furthermore, we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons. Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension. In rats, miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury. Our data reveal the mechanism for COS in axon regeneration, that is COS induce fibroblasts to produce TFAP2C-enriched EXOs, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1. Moreover, these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.
Beyond ecology: ecosystem restoration as a process for social-ecological transformation
Authors: Anazélia M. Tedesco, Sofía López-Cubillos, Robin Chazdon, Jonathan R. Rhodes, Carla L. Archibald, Katharina-Victoria Pérez-Hämmerle, Pedro H.S. Brancalion, Kerrie A. Wilson, Mariana Oliveira, Diego F. Correa, Liz Ota, Tiffany H. Morrison, Hugh P. Possingham, Morena Mills, Fabiane C. Santos, Angela J. Dean
Journal: Trends in Ecology & Evolution (2023)
Local targeting of TSLP: feat or defeat
Authors: Jérémy Charriot, Engi Ahmed, Arnaud Bourdin
Journal: European Respiratory Journal (2023)

The physiological role of airway smooth muscle remains highly elusive given the poor overall understanding of the regulatory elements and their influence in healthy humans [1]. Paradoxically, the pathophysiological contribution of airway smooth muscle contraction to asthma is better understood than the physiological role of this contraction in non-asthmatics: early and late asthmatic responses highlight immediate-immune cell-free and delayed-immune cell-dependent bronchoconstriction, respectively [2]. Reducing the late asthmatic response with the inhaled anti-TSLP antibody ecleralimab raises more questions than providing answers <https://bit.ly/3vOkEIN> We thank David Manley for revising the English in this editorial.
Comparison of two diagnostic intervention packages for community-based active case finding for tuberculosis: an open-label randomized controlled trial
Authors: Aliasgar Esmail, Philippa Randall, Suzette Oelofse, Michele Tomasicchio, Anil Pooran, Richard Meldau, Edson Makambwa, Lynelle Mottay, Shameem Jaumdally, Gregory Calligaro, Stuart Meier, Marianna de Kock, Tawanda Gumbo, Robin Mark Warren, Keertan Dheda
Journal: Nature Medicine (2023)
Polysubstance use and its correlation with psychosocial and health risk behaviours among more than 95,000 Norwegian adolescents during the COVID-19 pandemic (January to May 2021): a latent profile analysis
Authors: Rubén Rodríguez-Cano, George Kypriotakis, Laura Cortés-García, Anders Bakken, Tilmann von Soest
Journal: The Lancet Regional Health - Europe (2023)

Polysubstance use represents an adolescent health risk; however, large-scale studies investigating this issue during the COVID-19 pandemic are scarce. We aim to (i) characterise substance use profiles among adolescents and (ii) identify correlates of such substance use profiles.Norwegian nationwide survey data from 2021 were analysed using latent profile analysis. Participants were 97,429 adolescents aged 13-18. We assessed cigarette, e-cigarette and snus use, alcohol consumption, and cannabis and other illicit drug use. Correlates included psychosocial variables, health risk behaviours, and COVID-19-related problems.We identified three adolescent profiles; those who use no substances (n = 88,890; 91%); those who use snus and alcohol (n = 6546; 7%); and those who use multiple substances (i.e., polysubstance profile; n = 1993; 2%). Boys, older adolescents, adolescents with lower socio-economic status, and those reporting low levels of parental control, and higher parental alcohol use, mental health problems, pain-related variables, and other health risk behaviours were most likely to be in the polysubstance profile. Adolescents with social and mental health issues related to COVID-19 were more at risk of being in the polysubstance profile. Adolescents who use snus and alcohol showed similar patterns of risk factors, but on a somewhat lower level than those in the polysubstance profile.Adolescents who use multiple substances have an unhealthier lifestyle, are at a higher risk of experiencing psychosocial impairments, and report more problems related to the COVID-19 pandemic. Preventative strategies to reduce polysubstance use might help promote psychosocial well-being in adolescents across various life domains.This study was funded by two grants from the Research Council of Norway (project #: 288083 and 300816). The Norwegian Directorate of Health has funded the data collection. The Research Council of Norway and the Norwegian Directorate of Health have not had any role in study design, data collection, data analysis, interpretation, and writing of the report.
Hepatitis B virus infection in general practice across England: An analysis of the Royal College of General Practitioners Research and Surveillance Centre real-world database
Authors: Anna Maria Geretti, Harrison Austin, Giovanni Villa, Colette Smith, Caroline Sabin, Ruby Tsang, Julian Sherlock, Filipa Ferreira, Rachel Byford, Bernardo Meza-Torres, Martin Whyte, Simon de Lusignan
Journal: Journal of Infection (2023)
Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors
Authors: Luis Zapata, Giulio Caravagna, Marc J. Williams, Eszter Lakatos, Khalid AbdulJabbar, Benjamin Werner, Diego Chowell, Chela James, Lucie Gourmet, Salvatore Milite, Ahmet Acar, Nadeem Riaz, Timothy A. Chan, Trevor A. Graham, Andrea Sottoriva
Journal: Nature Genetics (2023)

Abstract In cancer, evolutionary forces select for clones that evade the immune system. Here we analyzed &gt;10,000 primary tumors and 356 immune-checkpoint-treated metastases using immune dN/dS, the ratio of nonsynonymous to synonymous mutations in the immunopeptidome, to measure immune selection in cohorts and individuals. We classified tumors as immune edited when antigenic mutations were removed by negative selection and immune escaped when antigenicity was covered up by aberrant immune modulation. Only in immune-edited tumors was immune predation linked to CD8 T cell infiltration. Immune-escaped metastases experienced the best response to immunotherapy, whereas immune-edited patients did not benefit, suggesting a preexisting resistance mechanism. Similarly, in a longitudinal cohort, nivolumab treatment removes neoantigens exclusively in the immunopeptidome of nonimmune-edited patients, the group with the best overall survival response. Our work uses dN/dS to differentiate between immune-edited and immune-escaped tumors, measuring potential antigenicity and ultimately helping predict response to treatment.
Rapid multiplex PCR for respiratory viruses reduces time to result and improves clinical care: Results of a systematic review and meta-analysis
Authors: Tristan W. Clark, Kristina Lindsley, Tara B. Wigmosta, Anil Bhagat, Rachael B. Hemmert, Jennifer Uyei, Tristan T. Timbrook
Journal: Journal of Infection (2023)

The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting.We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing.Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07).Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting.
Developmental trajectory of transmission speed in the human brain
Authors: Dorien van Blooijs, Max A. van den Boom, Jaap F. van der Aar, Geertjan M. Huiskamp, Giulio Castegnaro, Matteo Demuru, Willemiek J. E. M. Zweiphenning, Pieter van Eijsden, Kai J. Miller, Frans S. S. Leijten, Dora Hermes
Journal: Nature Neuroscience (2023)

Abstract The structure of the human connectome develops from childhood throughout adolescence to middle age, but how these structural changes affect the speed of neuronal signaling is not well described. In 74 subjects, we measured the latency of cortico-cortical evoked responses across association and U-fibers and calculated their corresponding transmission speeds. Decreases in conduction delays until at least 30 years show that the speed of neuronal communication develops well into adulthood.
Reply to: Central apnoeas, sympathetic activation and mortality in heart failure: look before you leap
Authors: Renaud Tamisier, Jean-Louis Pépin, Patrick Lévy
Journal: European Respiratory Journal (2023)

We thank C. Borrelli and co-workers for their interest in our manuscript reporting a randomised clinical trial (RCT) to investigate the effects on muscle sympathetic nerve activity (MSNA) when improving ventilation during sleep using adapted servo-ventilation (ASV) in patients suffering from chronic systolic heart failure with left ventricular ejection fraction below 45% (HFrEF) and central sleep apnoea (CSA) [1]. This work was a substudy of the SERVE-HF trial, the largest RCT conducted in patients with both CSA and HFrEF. It is not a cohort as reported in the letter from C. Borrelli and co-workers [2]. Sympathetic overactivity in chronic heart failure with central apnoea is a target to improve prognosis <https://bit.ly/3QHniK4>
Data privacy: a decade of confusion
Authors: Alison Stone, Chris Carrigan
Journal: BMJ (2023)

Iacobucci's article on a general practice withdrawing from a kidney screening pilot after patients voiced concerns emphasises the urgent need for clear guidance for practices and patients about the ways that patient data are used, including the purposes of direct care and secondary purposes. 1 We note that the practice chose to withdraw all of its patients from the kidney screening trial after objections from three patients.Questions or objections from patients should always be listened to and answered, but in this case the quick reaction to stop the pilot completely might not have been in the best interests of other patients in the practice.Practices are busy places and must rely on being able to access clear and up-to-date guidance about correct and proportionate uses of patient data to aid their role as data controllers of patient data.There is an urgent need for this guidance, both for practices and their patients.The guidance must explain the ways in which patient data are used for direct care, including when this care provision is contracted by the NHS to a commercial NHS partner.The guidance must also explain fully the different types of patient data opt-outs in England.Commercial partnerships for direct care are routine across many aspects of NHS services, including well established local breast screening being provided by a private medical company working closely with the NHS 2 and the targeted lung health check programme, delivered in partnership with the NHS. 3 If we are all to benefit from lifesaving interventions, guidance about permissive uses of our patient data for our care must be available to support our practice teams.It is alarming that, a decade on from the introduction of type 1 opt-outs, 4 there remains a clear lack of understanding of their purpose.
Dysbiosis of a microbiota–immune metasystem in critical illness is associated with nosocomial infections
Authors: Jared Schlechte, Amanda Z. Zucoloto, Ian-ling Yu, Christopher J. Doig, Mary J. Dunbar, Kathy D. McCoy, Braedon McDonald
Journal: Nature Medicine (2023)

Critically ill patients in intensive care units experience profound alterations of their gut microbiota that have been linked to a high risk of hospital-acquired (nosocomial) infections and adverse outcomes through unclear mechanisms. Abundant mouse and limited human data suggest that the gut microbiota can contribute to maintenance of systemic immune homeostasis, and that intestinal dysbiosis may lead to defects in immune defense against infections. Here we use integrated systems-level analyses of fecal microbiota dynamics in rectal swabs and single-cell profiling of systemic immune and inflammatory responses in a prospective longitudinal cohort study of critically ill patients to show that the gut microbiota and systemic immunity function as an integrated metasystem, where intestinal dysbiosis is coupled to impaired host defense and increased frequency of nosocomial infections. Longitudinal microbiota analysis by 16s rRNA gene sequencing of rectal swabs and single-cell profiling of blood using mass cytometry revealed that microbiota and immune dynamics during acute critical illness were highly interconnected and dominated by Enterobacteriaceae enrichment, dysregulated myeloid cell responses and amplified systemic inflammation, with a lesser impact on adaptive mechanisms of host defense. Intestinal Enterobacteriaceae enrichment was coupled with impaired innate antimicrobial effector responses, including hypofunctional and immature neutrophils and was associated with an increased risk of infections by various bacterial and fungal pathogens. Collectively, our findings suggest that dysbiosis of an interconnected metasystem between the gut microbiota and systemic immune response may drive impaired host defense and susceptibility to nosocomial infections in critical illness.
Association of dipeptidylpeptidase 4 (<scp>CD26</scp>) with chondrocyte senescence and radiographic progression in knee osteoarthritis: comment on the article by Chen et al
Authors: An‐Fang Huang, Wang‐Dong Xu
Journal: Arthritis & Rheumatology (2023)

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